This project will investigate the metabolic activity, mechanism of action and bioactive compounds of Shilianhau (SLH). SLH is a crude extract of a single plant Sinocrassula indica berger. The commercial product of SLH is popular in US dietary supplement market for the control of blood glucose. However, its efficacy and mechanism of action has not been well characterized. In our preliminary studies, several popular botanical supplements were tested in a dietary obesity animal model. The result suggests that SLH is the most potent botanical product with glucose lowering actions. More importantly, SLH exhibited a novel anti-obesity activity independent of food intake. This suggests that SLH may prevent obesity by promoting energy expenditure. In the mechanistic study, SLH was found to induce production of adiponectin, activate serine kinase p38 and fat oxidation. This further supports the energy expenditure effect of SLH. In the regulation of carbohydrate metabolism, SLH inhibited activation of IKK/NF-kB and stimulated insulin secretion in the beta-cells. This suggests that SLH may enhance insulin action by protecting insulin sensitivity and increasing insulin level. Based on these preliminary data, we hypothesize that SLH controls obesity and glucose metabolism by stimulating energy expenditure and insulin action. We will test this hypothesis through three specific aims: (1) To investigate the role of energy expenditure in the antiobesity activity of SLH; (2) To identify the molecular mechanism by which SLH enhances insulin action; (3) To standardize SLH bioactive components through bioassay-guided fractionation. In this project, expertise, resources and knowledge from several investigators will be joined together to study the metabolic activities of SLH. Results from the study will lead to a significant advance in our understanding of cellular and molecular mechanism of SLH in the regulation of fat and glucose metabolism.